Fixed-Dose HCV Combo OK With Ribavirin Substitute

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this small trial demonstrated much better HCV virologic response when ribavirin or another investigational agent were added to a combination pill of sofosbuvir/ledipasvir than when the combo pill was used alone.

Be aware that neither ledipasvir or the combination pill is FDA approved for HCV treatment.

WASHINGTON -- A fixed-dose combination of two investigational hepatitis C (HCV) drugs needs a boost in patients with advanced fibrosis or cirrhosis, a researcher said here.

In the ELECTRON trial, Gane and colleagues are testing a single-pill combination of sofosbuvir, a nucleotide polymerase inhibitor, and ledipasvir, which blocks the nonstructural NS5A protein.

For this analysis, he reported outcomes in previously treated patients with genotype 1 HCV and advanced fibrosis or cirrhosis, who were given 12 weeks of the fixed-dose combination alone or with either ribavirin or GS-9669, a NS5B non-nucleoside inhibitor.

The primary endpoint was the proportion of patients who had undetectable virus 12 weeks after the end of therapy (SVR12).

Initially, Gane said, the researchers had tested the fixed-dose pill in 20 patients with or without ribavirin, but results were disappointing without ribavirin with SVR12 rates of 70% versus 100%.

So they enrolled another 51 patients and randomly assigned them to 12 weeks of the fixed dose combination along with either ribavirin or GS-9669.

The results here were better, Gane reported, as the SVR12 rate was 100% in both groups.

Importantly, patients receiving GS-9669 did not have the typical drop in hemoglobin that is associated with ribavirin.

In another sub-study, researchers tested the effect of the combination, along with ribavirin, in 25 treatment-naïve genotype 1 patients for only 8 weeks of treatment.

One advantage of many of the all-oral regimens under investigation is that they are quickly beneficial, with treatment duration of usually 12 or 24 weeks.

In contrast, treatment with the current standard of care -- pegylated interferon, ribavirin, and a protease inhibitor -- can be as long as 48 weeks.

In another study to be presented here, Gane said, 8 weeks of sofosbuvir, ledipasvir, and ribavirin was as efficacious as 12 weeks.

But a 6-week treatment period was too short, he said, and led to an "unacceptable relapse rate."

Both at 12 and 8 weeks, Gane said, the three drugs yielded 100% SVR12 rates, but after the 6-week course only 68% of patients reached that endpoint.

The analyses begin to fill in the picture of how the fixed-dose combination might be used, commented Gary Davis, MD, of Baylor University Medical Center in Waco, Texas, who was not involved in the study but who moderated the session at which it was presented.

But the studies remain small so they don't know how much stock can be put in them, he told MedPage Today.